Recent studies on a variety of organisms have shown that the pancreatic islets are innervated. However, there have been no studies directed at answering the question of the role of this innervation in islet endocrine cell secretion. The innervating fibers appear basically as two types, adrenergic and cholinergic, with variations apparent in different species. The main objective of the proposed work is to elucidate the role of this innervation in insulin release. Two approaches to the problem will be followed: 1) Islets will be denervated surgically and then transplanted autoplastically or homoplastically; 2) Chemical denervation will be attempted with 6-hydroxydopamine and/or with Hemichalinium. It is expected that the effects of denervation upon insulin release will depend upon the nature of the nerve fibers impinging upon the B-cells. The teleost, Gillichthys mirabilis, will be used in this study because specimens are obtainable in large numbers, they are easy to maintain, and have large principal islets which are ideally suited for transplantation studies. Islets will be studied histologically to determine cell types present and histochemically with the Falck fluorescence technique for the demonstration of monoaminergic nerve fibers. A method for the demonstration of acetylcholinesterase activity will also be employed. Radioimmunoassay of insulin will be carried out in vivo. Incubations of surgically or chemically-denervated islets will be performed with a variety of substrates known to affect insulin release and the media similarly assayed for insulin.